Methamphetamine (MA) abuse among adolescents is a significant public health problem that is associated with psychological distress, depressive symptoms, auditory hallucinations, suicidal ideation, and high rates of violent behavior and HIV-related sexual risk behaviors. There are currently no effective medications for MA abuse available, although results from two preliminary randomized placebo-controlled trials of bupropion for MA dependent adults found bupropion to be more effective than placebo, but only among participants who reported low frequency MA use at baseline. Adolescent MA abusers are likely to have shorter MA use histories and therefore may respond to bupropion similarly to adults with baseline lower frequencies of MA use. As a result, bupropion represents an ideal candidate to evaluate as a pharmacotherapy for MA abuse among adolescents. Yet since no studies have examined pharmacotherapies for MA abuse among adolescents, a pilot study to assess the safety, tolerability, and acceptability of bupropion among adolescents with MA abuse and to optimize clinical trial methods for use with this population is needed before launching a full-scale clinical trial. Therefore we propose a pilot study to address the following specific aims: (1) To assess the feasibility of a randomized, double-blind clinical trial of bupropion versus placebo, in conjunction with cognitive behavioral therapy and contingency management targeting attendance, among adolescents with MA abuse, as assessed by rates of enrollment, compliance with study procedures including medication adherence, and retention. (2) To describe the safety and tolerability of bupropion compared to placebo among adolescents with MA abuse, as determined by the frequency and severity of adverse events for each condition. (3) To evaluate the utility of a novel recruitment method for recruiting adolescent MA abusers to the trial using a peer-referral strategy that is a variant of Respondent Driven Sampling. To achieve the objectives of this pilot study, we will enroll 30 adolescents (aged 14-21) seeking treatment for MA abuse who will be randomly assigned to receive treatment with bupropion extended release (XL) 300 mg once a day (n=20) or placebo once a day (n=10), in conjunction with cognitive behavioral therapy and contingency management targeting attendance, for 8 weeks followed by a 4 week follow-up period. The use of once daily dosing of bupropion XL is justified by pharmacokinetic studies in adolescents and may increase medication adherence. Participant safety, including possible suicidal ideation/behavior, will be monitored closely via a battery of clinical assessments throughout the trial. Additional exploratory efforts will provide formative data concerning the clinical characteristics of adolescents entering a MA medication clinical trial, including baseline frequency of MA use and prevalence of psychiatric disorders particularly ADHD, and will assess changes in ab libitum cigarette smoking during treatment. Results of the study are essential to designing a phase II clinical trial adequately powered to determine the efficacy of bupropion for MA abuse among adolescents. PUBLIC HEALTH RELEVANCE: Methamphetamine (MA) abuse among adolescents is a significant public health problem that is associated with psychological distress, depressive symptoms, auditory hallucinations, suicidal ideation, and high rates of violent behavior and HIV-related sexual risk behaviors. No studies have examined pharmacotherapies for MA abuse among adolescents, and therefore studies to identify effective pharmacotherapies for adolescents with MA abuse are urgently needed. The proposed pilot study has significant public health relevance in that it will provide critical data required for the design and implementation of a full scale clinical trial of bupropion, a medication that has shown efficacy for MA dependence in adults, for MA abuse in adolescents.